Symbiosis with Ancient Viruses Critical for Human Development

Human blastocysts don’t develop when ancient virus RNA, “trapped” in our DNA for millions of years, is artificially blocked.

In recent years humans have come to understand we are not just about Darwinian natural selection, but symbiosis. For two billion years, there were only bacteria and archaea. Then a single archaea swallowed a bacteria in such a way the bacteria became its powerpack. Complex life exploded out of this symbiosis.

Remnants of that moment are alive in humans today: experimental and genetic analysis proves the power packs of our cells, mitochondria, are indeed ancestors of those ancient bacteria.

This week a Stanford University crew reported in Nature Genetics making another key symbiosis finding: human embryos need ancient viral RNA, trapped in the non-protein-coding regions of our genomes, to grow. They are essential for our existence.

Those ancient viral RNA “were acquired in the primate lineage, some millions of years ago, by infection/insertion into the germ-cell lineage that gives rise to eggs and sperm,” developmental biologist Renee Reijo Pera, Ph.D., told Bioscience Technology. Reijo Pera, co-senior author on the study, is now vice president for research and economic development at Montana State University. “Our development without them would have been fundamentally different. Different species likely all use their own sequences. To the best of our knowledge, there are no other data to show that single non-coding, human-specific, retrovirally derived genes are essential for timing or cell fate decisions in human development. We were very surprised by the results.”

Harvard University/Massachusetts Institute of Technology geneticist John Rinn, Ph.D., told Bioscience Technology that function was earlier linked to some retroviral RNA elements found in isolated stem cells, and induced pluripotency. But he agreed that, until now, a seminal role was not found for those elements in actual human development: “This manuscript makes significant progress in understanding the functional roles of ERV-lncRNA [endogenous retroviral long-coding RNA].” Rinn was uninvolved in the work.

“The paper is interesting because it is one of the first to probe the role of long non-coding RNA— a relatively poorly understood class of regulatory RNAs— in early human development and pluripotency,” Harvard stem cell researcher George Daley, M.D., Ph.D., told Bioscience Technology. Daley, director of the Dana Farber Cancer Institute/Boston Children’s Hospital Stem Cell Transplantation Program, made some early lncRNA finds with Rinn. He was also uninvolved in the new work.